Intimal hyperplasia is a common pathological condition which develops after various forms of injury to blood vessels including sutured anastomoses, angioplasty, and stenting. Intimal hyperplasia may lead to blood vessel stenosis or occlusion and the potential clinical sequellae include limb loss, stroke, myocardial infarction, or death. Currently there is no effective means to control this pathological process. Our laboratory (in an animal model of a synthetic vascular graft to artery anastomosis) has demonstrated: 1) creation of an anastomosis results in a decrease in oxygen delivery to the artery wall which normalizes in 42 days, and 2) supplemental oxygen for 42 days effectively reverses the artery wall hypoxia, inhibits smooth muscle cell proliferation, and prevents the formation of intimal hyperplasia. This project will determine if the findings from our animal model are applicable to the human condition. We have chosen to examine the development of intimal hyperplasia at the arterial and venous anastomoses of synthetic hemodialysis grafts in humans because end stage renal disease affects 200,000 individuals annually with 60 percent requiring hemodialysis access. Intimal hyperplasia is the leading cause of hemodialysis access failure, is easy to measure non-invasively, and we are able to accurately follow this patient group. We will also begin an investigation into the role of oxidative stress in hypoxia induced intimal hyperplasia. The results of this project will lead to a simple, safe, and effective method to control intimal hyperplasia in humans-the short administration of supplemental oxygen. The results of this project will have wide-spread application for the largest growing segment of the population-the segment most likely to undergo any form of blood vessel intervention including bypass grafting, angioplasty, and stenting.